NDRG 2 gene is expressed in various kinds of tissue cells such as brain, muscle or kidney cells (Qu, et al., Mol Cell Biochem., 229: 35-44, 2002; Kokame, et al., J. Biol. Chem., 271: 29659-29665, 1996; Ulrix, et al., FEBS Lett., 455: 23-26, 1999). It is reported that the NDRG gene may be classified to 4 different kinds. The NDRG genes have a high homology and are differentially expressed according to the development and growth of each individual. In detail, NDRG 1 gene is expressed relatively in overall tissues and cells. In contrast, NDRG 2 gene and NDRG 3 gene are expressed in brain, heart, muscle and kidney cells. NDRG 4 gene is expressed exclusively in brain and heart. Therefore, it is predicted that the NDRG genes might play different roles one another. But, there are not reports elucidating the exact functions of the genes yet.
On the other hand, dendritic cell, an antigen-presenting cell (APC) is essential to regulate a function of immune cells. The dendritic cell is a peculiar immune cell stimulating a naive T cell to induce a primary immune response. Therefore, it is actively attempted to investigate the action of dendritic cells in infectious diseases and tumor immunity. Especially in intractable diseases, genomic studies on a dendritic cell elucidating its biological function is tried to develop a vaccine applying the dendritic cell to induce a specific immunity. Recently, it is proved that the dendritic cell has a remarkable anticancer efficacy by injecting with a NK cell. Therefore, the mature dendritic cell and the NK cell may play an important role to develop a therapeutic drug using cells. In order to maximize the efficacy of the therapeutic drug, it is necessary to develop markers for this mature dendritic cell.
However, there are several problems. It is difficult to collect dendritic cells in a large scale. Further, any specific marker existing in this cell is not found, yet. Either in a clinical field, the characteristics of the dendritic cell is not fully understood. Accordingly, it is required to investigate the characteristics of the dendritic cell deeply, screen specific genes or proteins expressed in this cell and recognize their functions. Indeed, the dendritic cells may be used to treat and prevent various diseases by effective therapy.
The present inventors have already found that the NDRG 2 gene is specifically expressed in a dendritic cell differentiated from a monocyte of human peripheral blood. The NDRG 2 gene was isolated and then, introduced to a hybridoma cell line to prepare the polyclonal antibody against the NDRG 2 protein. This result has been publicly disclosed. (International Patent Application PCT/KR2004/000634; Choi, S. C. et al., FEBS Lett., 553(3): 413-418, 2003)
In addition, it is reported that the NDRG 2 might be a cancer suppressor gene participating in carcinogenesis. Also, the cancinogenic cell is elucidated to reduce the gene expression of NDRG 2, and especially decrease highly in a malignant tumor. In detail, it is recognized that the expression of the NDRG 2 is reported to decrease remarkably in aggressive meningioma by conducting a genomic analysis. (Lusis, E. A. et al, Cancer Res., 65: 7121-6, 2005) The mRNA amount of the NDRG 2 is also reduced in liver cancer and pancreas cancer markedly. (Hu, X. L. et al., World J. Gastroenterol., 10: 3518-21, 2004). Therefore, it is expected that the NDRG 2 protein is used to treat cancers by regulating its gene expression, because reducing in carcinogenic cells notably and being focused as a cancer suppressor gene.
Nevertheless, studies on the NDRG 2 are lacked and just starting. Especially, it is required to develop a monoclonal antibody specific for the NDRG 2 protein and a method for measuring a quantity of the NDRG 2.
Since manufacturing the polyclonal antibody, the present inventors have already used it to investigate the characteristics of the dendritic cell (International Patent Application PCT/KR2004/000634; Choi, S. C. et al., FEBS Lett., 553(3): 413-418, 2003). In practice, the NDRG 2 protein is measured in cells or tissues qualitatively by performing a Western blot or immuno-staining. However, there are several limitations. This immuno-staining is hardly conducted in the tissue due to a high background etc.
In order to settle above-mentioned problems, the present inventors have tried to develop a monoclonal antibody specific for the NDRG 2 protein, a cell line producing the monoclonal antibody, a method for measuring a quantity and quality of NDRG 2 protein, and a protein chip using the same that is necessary to investigate the NDRG 2 expressed in a dendritic cell and its function in a cancer cell and completed the invention successfully.